The microsomal mixed-function oxidase (MFO) system of mammals exhibits species, sex, and tissue variations. Treatment of animals with various pharmaceutical agents, environmental pollutants, and other exogenous compounds can bring about changes in the MFO system(s). Both stimulation and inhibition of these systems can be elicited, and in some cases this can be accomplished with the same compound. It is not understood if these changes are due to direct effects on the major components of the MFO, to alterations in the membrane environment, or to changes in the concentrations or kinds of endogenous compounds that interact with the MFO. The objective of this project is to increase our understanding of the factors responsible for the variances noted among mixed-function oxidase systems from diferent sources. This objective is being pursued via several approaches: 1. Tissue Differences: The MFO systems from rabbit liver and lung are being solubilized and separated into their component parts. These components (cytochrome P-450, TPNH cytochrome c reductase and lipid) and the enzymatic activities obtained by component recombination are being compared. 2. Cytochrome P-450 Differences: Rabbit pulmonary and hepatic cytochrome P-450's are being purified and compared. 3. Differences in Response to In Vivo Treatment: The effects of in vivo administration of 3-methylcholanthrene (3-MC) on the MFO in adult rabbit and rat liver are being studied.